Studies are proposed to test our hypothesis that premature atherosclerosis in the diabetic is a consequence of enhanced platelet sensitivity to aggregation, and vessel wall susceptibility to oxidative damage and platelet adhesion. We will study platelet cyclooxygenase, thromboxane synthetase and lipoxygenase in normal and diabetic rabbits since these enzymes synthesize oxygenated fatty acid derivatives that initiate platelet aggregation. We will also study arterial prostacyclin synthetase activity of the diabetic animal since this enzyme defends the vessel wall against oxidative damage and platelet clumping. We will study the effect of vitamin E on platelet function and vessel wall metabolism in the normal and diabetic animal.